Behaviour change interventions to improve physical activity in adults: a systematic review of economic evaluations.

BACKGROUND: Behaviour change interventions can result in lasting improvements in physical activity (PA). A broad implementation of behaviour change interventions are likely to be associated with considerable additional costs, and the evidence is unclear whether they represent good value for money. The aim of this study was to investigate costs and cost-effectiveness of behaviour change interventions to increase PA in community-dwelling adults. METHODS: A search for trial-based economic evaluations investigating behaviour change interventions versus usual care or alternative intervention for adults living in the community was conducted (September 2023). Studies that reported intervention costs and incremental cost-effectiveness ratios (ICERs) for PA or quality-adjusted life years (QALYs) were included. Methodological quality was assessed using the Consensus Health Economic Criteria (CHEC-list). A Grading of Recommendations Assessment, Development and Evaluation style approach was used to assess the certainty of evidence (low, moderate or high certainty). RESULTS: Sixteen studies were included using a variety of economic perspectives. The behaviour change interventions were heterogeneous with 62% of interventions being informed by a theoretical framework. The median CHEC-list score was 15 (range 11 to 19). Median intervention cost was US$313 per person (range US$83 to US$1,298). In 75% of studies the interventions were reported as cost-effective for changes in PA (moderate certainty of evidence). For cost per QALY/gained, 45% of the interventions were found to be cost-effective (moderate certainty of evidence). No specific type of behaviour change intervention was found to be more effective. CONCLUSIONS: There is moderate certainty that behaviour change interventions are cost-effective approaches for increasing PA. The heterogeneity in economic perspectives, intervention costs and measurement should be considered when interpreting results. There is a need for increased clarity when reporting the functional components of behaviour change interventions, as well as the costs to implement them.

Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism.

Colon and rectal cancer: An emergent public health problem.

Colorectal cancer ranks third globally, with a high mortality rate. In the United States, and different countries in Europe, organized population screenings exist and include people between 50 and 74 years of age. These screenings have allowed an early diagnosis and consequently an improvement in health indicators. Colon and rectal cancer (CRC) is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality. This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology, as well as a diagnosis of the epidemiological situation of CRC. Finally, the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

Special Issue on Cancer Smart Nanomedicine.

In this Special Issue entitled "Cancer Smart Nanomedicine", we have gathered high-quality contributions related to the fascinating field of nanomedicine [...].

Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation.

AIMS: Breast cancer (BC) presents high mortality rate and about 25-46 % have mutation in the PIK3CA gene. Alpelisib is a PI3K inhibitor that acts on p110α, which is a subunit of the PI3K protein. The melatonin shown important anti-neoplastic effects and may increase the effectiveness of chemotherapy. This study evaluated the synergistic action of Alpelisib and Melatonin in BC lines carrying the H1047R mutation in PIK3CA, relative to the cellular dynamics and the PI3K/AKT/mTOR pathway. MAIN METHODS: MDA-MB-468 (triple-ernegative), MDA-MB-453 (H1047R PIK3CA, HER2+) and T-47D cells (H1047R PIK3CA, ER+/PR+) were divided into four treatment groups: control; Melatonin (1 mM); Alpelisib (1 µM); and Alpelisib (1 µM) + Melatonin (1 mM). Cell viability and migration were investigated using the MTT assay and Transwell assay, respectively. Protein expression of PI3K, p-AKT, mTOR, HIF-1α, and caspase-3, was verified using immunocytochemistry. KEY FINDINGS: MTT assay revealed that MDA-MB-453 and T-47D showed reduction in cell viability in all groups, especially in the MDA-MB-453 treated with Melatonin + Alpelisib. MDA-MB-468 presents reduction in cell migration only with Melatonin, while in the lines with mutation, the treatment of Melatonin + Alpelisib caused inhibition of cell migration. PI3K, p-AKT, mTOR and HIF-1α were inhibited after treatment with Melatonin + Alpelisib in MDA-MB-453 and T-47D lines. The expression of caspase-3 increased in all groups in MDA-MB-453 and T-47D cells, being the increase more pronounced in the Melatonin + Alpelisib group. SIGNIFICANCE: These results indicate that the combined use of Melatonin and Alpelisib may be more effective in inhibiting BC in women carrying the PIK3CA gene mutation than either treatment alone.

R2CHA2DS2-VA Predictsthe Cardiovascular Risk after Carotid Endarterectomy.

BACKGROUND: R2CHA2DS2-VA score has been used to predict short and long-term outcomes in many cardiovascular diseases. This study aims to validate the R2CHA2DS2-VA score as a long-term major adverse cardiovascular events (MACE) predictor after carotid endarterectomy (CEA). Secondary outcomes were also assessed regarding the incidence of all-cause mortality, acute myocardial infarction (AMI), major adverse limb events (MALE), and acute heart failure (AHF). METHODS: From January 2012 to December 2021, patients (n = 205) from a Portuguese tertiary care and referral center that underwent CEA with regional anesthesia (RA) for carotid stenosis (CS) were selected from a previously collected prospective database, and a posthoc analysis was performed. Demographics and comorbidities were registered. Clinical adverse events were assessed 30 days after the procedure and in the subsequent long-term surveillance period. Statistical analysis was performed by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of the patients enrolled, 78.5% were males with a mean age of 70.44 ± 8.9 years. Higher scores of R2CHA2DS2-VA were associated with long-term MACE (adjusted hazard ratio (aHR) 1.390; 95% confidence interval (CI) 1.173-1.647); and mortality (aHR 1.295; 95% CI 1.08-1.545). CONCLUSIONS: This study demonstrated the potential of the R2CHA2DS2-VA score to predict long-term outcomes, such as AMI, AHF, MACE, and all-cause mortality, in a population of patients submitted to carotid endarterectomy.

Therapeutic Potential of Genistein: Preclinical Studies, Clinical Evidence, and Nanotechnology Application.

Genistein (4',5,7-trihydroxyisoflavone) is a natural plant-derived phytoestrogen that can be found, for example, in soybean seeds. Genistein is present mainly in the human diet and is a common precursor in the antimicrobial phytoalexins biosynthesis and phytoanticipins in vegetables. The interest in genistein has increased due to its pharmacological effects, including anti-cancer activity, neuroprotective effects, cardiovascular protection, anti-inflammatory effects, antioxidant activity, and prevention of obesity. The most challenging issue for improving genistein is its low oral bioavailability, which has led to many animal and human pharmacokinetic studies and numerous clinical trials. Several drug delivery systems have been developed to protect and stabilize genistein to overcome the challenge of low bioavailability. This work concerns a revision of the literature reporting nano and microformulations for genistein encapsulation, including lipid nanoparticles, liposomes, tocotrienol-rich nanoemulsions, polymeric nanoparticles, dextran complexes, chitosan complexes, and Fe3O4 nanoparticles with carboxymethylated chitosan. Regarding the enormous potential of genistein, several clinical trials and marketed formulations can be found in the market.

Epigallocatechin-3-gallate Delivered in Nanoparticles Increases Cytotoxicity in Three Breast Carcinoma Cell Lines.

The anticancer activity of epigallocatechin-3-gallate (EGCG), orally administrated, is limited by poor bioavailability, absorption, and unpredictable distribution in human tissues. EGCG charged nanoparticles may represent an opportunity to overcome these limitations. We assayed two different kinds of lipid nanoparticles (LNPs and LNPs functionalized with folic acid) charged with EGCG on three breast carcinoma cell lines (MCF-7, MDA-MB-231, and MCF-7TAM) and the human normal MCF10A mammary epithelial cells. Both LNPs loaded with EGCG, at low concentrations, induced a significant cytotoxicity in the three breast carcinoma cells but not in MCF10A cells. In view of a future application, both LNPs and LNPs-FA were found to be very suitable for in vitro studies and useful to improve EGCG administration in vivo. Since they are produced by inexpensive procedures using bioavailable, biocompatible, and biodegradable molecules, they represent an applicable tool for a more rationale use of EGCG as an anti-cancer agent.

Diet quality index and its components have not associated with the development of breast cancer risk assessed by the diet quality index: a case-control study.

OBJECTIVE: To investigate if the diet quality and its components are associated with breast cancer risk. METHODS: A case-control study was conducted with 332 women, 114 who were diagnosed with breast cancer, and 218 control individuals. Groups were matched for age, body mass index, and menopausal status. The quality of diet was assessed using Brazilian Healthy Eating Index Revised (BHEI-R) and its components. Food consumption was measured through three 24-h dietary recalls and assessed using the NDS-R software. For statistical analyses, it was performed an adjusted logistic regression, estimation of the Odds Ratio (OR), and 95% confidence interval (95%CI), with a p-value <0.05. RESULTS: The BHEI-R score, classified into quartiles, did not differ between groups in the lowest quartile of diet quality (p=0.853). The components total cereals (p=0.038), saturated fat (p=0.039) and Gord_AA (fat, alcohol, and added sugar) (p=0.023) had higher scores among the case group. The scores for total fruits (p=0.010) and milk and dairy products (p=0.039) were higher among the control group. The BHEI-R components and the quality of diet were not associated with the outcome. CONCLUSION: Diet quality, assessed by the BHEI-R and its components, was not associated with breast cancer.

Otimização das etapas de confecção do protocolo Branemark com carga tardia utilizando o guia multifuncional / Optimization of the Branemark protocol late load preparation steps using the multifunctional guide

O "planejamento reverso" em implantodontia busca alcançar um melhor prognóstico para a reabilitação do paciente, permitindo uma maior previsibilidade para o tratamento a partir do momento em que se planeja a reabilitação oral protética antes mesmo de planejar os implantes osseointegráveis. O dispositivo de resina acrílica chamado guia multifuncional representa a disposição final dos dentes na reabilitação e auxilia demasiadamente na etapa protética em casos em que não é possível a carga imediata. Ainda, otimiza o número de consultas do tratamento pois orienta a relação maxilomandibular, dimensão vertical e correta posição dos dentes. O presente trabalho tem como objetivo apresentar um caso clínico da utilização do guia multifuncional para moldagem dos implantes em caso de protocolo Branemark com dois tempos cirúrgicos, mostrando sua utilidade para diminuição do número de consultas na etapa de confecção da prótese total inferior definitiva. Diante dos resultados obtidos na realização do caso, foi possível concluir que nos casos de protocolo Branemark quando não é possível realizar a carga imediata, o guia multifuncional pode ser aproveitado e utilizado com sucesso, para a moldagem e confecção da prótese definitiva, diminuindo o número de consultas e otimizando o tratamento.

Reverse planning in implantology aims to improve patient's rehabilitation prognosis allowing greater treatment predictability from the prosthetic planning and before the implants installation. The acrylic resin device called multifunctional guide represents the final teeth disposition and is very useful in the prosthetic step when immediate loading is not possible. And it optimizes appointments treatment number since it guides the maxillomandibular relation, vertical dimension and correct teeth position. The aim of this study was to present a clinical case using the multifunctional guide for implant molding a two steps Branemark protocol, showing its usefulness to reduce the appointments number during the inferior total denture preparation step. Based on these results, it was possible to conclude that in Branemark protocol, when it immediate loading is not possible, the multifunctional guide can be used successfully for molding and making the final prosthesis, reducing the number of visits and optimizing treatment.

Implante transitório de corpo único com ativação imediata para retenção de prótese total provisória - relato de caso / Single body transient implants immediate activated for provisional prosthesis retention ­ case report

A reabilitação protética ganhou um componente que veio solucionar problemas de pessoas edentadas que até então pareciam sem solução. Trata-se dos implantes osseointegráveis, introduzidos pelo professor Per Ingvar Branemark entre os anos 70 e 80, e que, nos dias de hoje, se tornou na maioria dos casos, a primeira opção para a reabilitação oral. No caso de edentados totais na mandíbula, a prótese total fixa sobre implantes instalados entre os forames mentuais é um tipo de tratamento reabilitador com elevado grau de sucesso. Nos casos onde não é possível a colocação da prótese fixa com carga imediata após a instalação dos implantes, o paciente pode usar uma prótese total provisória, diretamente sobre os implantes permanentes instalados ou retida por implantes transitórios de corpo único, com encaixe tipo bola/o'ring. O presente artigo relata um caso clinico com utilização de implantes transitórios de corpo único para reter prótese total provisória, durante o tempo da osseointegração dos implantes permanentes.

Prosthetic rehabilitation gained a component that solved problems of edentulous people. These are the Osseo integrative implants, introduced by Professor Per Ingvar Branemark between the 1970s and 1980s, and which has become in most cases the first option for oral rehabilitation. In the case of mandible total edentulous, the total fixed prosthesis on implants installed between the mental foramina is a type of rehabilitation treatment with a high degree of success. In cases where it is not possible to place the fixed prosthesis with immediate loading after implant installation, the patient may use a provisional total prosthesis, directly on the permanent implants installed or retained by transient implants of single body, ball-type fitting 'ring. The present article reports a clinical case with the use of single body transient implants to retain temporary total prosthesis during the time of osseointegration of permanent implants.

Economic evaluation of physical activity mass media campaigns across the globe: a systematic review.

BACKGROUND: Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. METHODS: A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. RESULTS: Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. CONCLUSIONS: There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. REVIEW REGISTRATION: https://bit.ly/3tKSBZ3.

Impact of physical activity programs and services for older adults: a rapid review.

BACKGROUND: Knowledge of which physical activity programs are most effective for older adults in different sub-populations and contexts is limited. The objectives of this rapid review were to: 1) Overview evidence evaluating physical activity programs/services for older adults; and 2) Describe impact on physical activity, falls, intrinsic capacity (physical domain), functional ability (physical, social, and cognitive/emotional domains), and quality of life. METHODS: We conducted a rapid review of primary studies from 350 systematic reviews identified in a previous scoping review (March 2021: PEDro, MEDLINE, CINAHL, Cochrane Database). For Objective 1, we included intervention studies investigating physical activity programs/services in adults ≥ 60 years. Of these, we included good quality (≥ 6/10 PEDro scale) randomised controlled trials (RCTs) with ≥ 50 participants per group in Objective 2. RESULTS: Objective 1: Of the 1421 intervention studies identified from 8267 records, 79% were RCTs, 87% were in high income countries and 39% were good quality. Objective 2: We identified 87 large, good quality RCTs (26,861 participants). Overall activity promotion, structured exercise and recreation/sport had positive impacts (≥ 50% between-group comparisons positive) across all outcome domains. For overall activity promotion (21 intervention groups), greatest impacts were on physical activity (100% positive) and social outcomes (83% positive). Structured exercise (61 intervention groups) had particularly strong impacts on falls (91% positive), intrinsic capacity (67% positive) and physical functioning (77% positive). Recreation/sport (24 intervention groups) had particularly strong impacts on cognitive/emotional functioning (88% positive). Multicomponent exercise (39 intervention groups) had strong impacts across all outcomes, particularly physical activity (95% positive), falls (90% positive) and physical functioning (81% positive). Results for different populations and settings are presented. CONCLUSION: Evidence supporting physical activity for older adults is positive. We outline which activity types are most effective in different populations and settings.

Nanomedicine for the Delivery of RNA in Cancer.

The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous scientific breakthroughs, we have witnessed exponential growth in the elucidation of mechanisms that underlie carcinogenesis and metastasis. The development of more selective therapies made it possible to improve cancer treatment. Although interdisciplinary research leads to encouraging results, scientists still have a long exploration journey. RNA technology represents a promise as a therapeutic intervention for targeted gene silencing in cancer, and there are already some RNA-based formulations in clinical trials. However, the use of RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Thus, the use of nanomedicine employing nanoparticles to encapsulate RNA may represent a suitable platform to address the major challenges hampering its therapeutic application. In this review, we have revisited the potential of RNA and RNA-associated therapies to fight cancer, also providing, as support, a general overview of nanoplatforms for RNA delivery.

Epigallocatechin-3-Gallate Delivery in Lipid-Based Nanoparticles: Potentiality and Perspectives for Future Applications in Cancer Chemoprevention and Therapy.

Chemoprevention is a strategy aimed to not only reduce the risk but also delay the development or recurrence of cancer. An ideal chemopreventive agent is not dangerous and ought not to result in side effects or damage to human health. In this context, epigallocatechin-3-gallate (EGCG) is considered a suitable chemopreventive agent, but its clinical use is limited by many factors, namely, the difference in source, administration, individual metabolism, absorption, and distribution. Genetic and dietary differences greatly cause this variability, which has limited the rational use of EGCG in chemoprevention and, particularly, the definition of a safe and efficient concentration. In the present mini review, the main limitations to a complete understanding of the use of EGCG as a chemopreventive agent will be briefly illustrated. This review also indicates the introduction and trialing of lipid-based nanoparticles (NPs) as a proper strategy to deliver EGCG at a well-defined concentration for better investigation of the chemopreventive activity. Finally, some examples of cancers that might benefit from EGCG treatment in different stages of the disease are proposed.

MANAGEMENT OF THE UPPER LIMB ARTERIOVENOUS MALFORMATIONS.

Arteriovenous malformations (AVMs) involving the upper limb constitute 10% of the total AVMs. In the upper limb, AVMs are more frequent in the hand than in the arm, being the hand one of the body's regions more frequently associated with AVMs, coming after the head and neck. The total prevalence of the upper limb AVMs remains unknown and there is currently no definitive consensus for the treatment of upper limb AVMs. The purpose of this study was to review the best evidence of the treatment for the upper limb AVMs and describe their clinical characteristics and diagnosis. The majority of patients with asymptomatic AVMs follows a conservative management. In the symptomatic patients, the treatment with surgery and or chemical embolization is beneficial. The amputation can be necessary in the case of life-threatening and massive AVMs, constituting the first step in patient's rehabilitation. Although the most common option for the management of symptomatic or functional AVMs is the embolo-sclerotherapy combined with surgery, different outcomes should be taken into account to plan the treatment, specially the presence of symptoms, bleeding and heart failure.

Treatment of Triple Negative Cell Lines with Olaparib to Block DNA Repair.

BACKGROUND: The most aggressive breast cancer is the triple negative histological type, and the gold standard for its treatment is platinum salts, such as carboplatin. Due to high recurrence, there is a need to test new drugs, such as PARP inhibitors (PARPi), that induce lethality in cells with DNA damage. Olaparib is a PARPi, already used in some tumors but not tested in canine species. Thus, the aim of this study was to demonstrate the efficacy of olaparib in inhibiting DNA repair and control disease progression by decreasing the migration capacity of mammary tumor cells. METHODS: The cell lines CF41.Mg and MDA-MB-468 were cultured and MTT was performed to define the best dose of carboplatin. Next, the cells were treated with 10 µM carboplatin, olaparib, and with a combination of both for 24 hours. PARP-1 protein and gene expression were evaluated by immunofluorescence, western blotting, and qRT-PCR, respectively. The analysis of cell migration was performed in transwell chambers. RESULTS: For CF41.Mg and MDA-MB-468 cell lines, there was a decrease in PARP-1 protein and gene expression after treatment with carboplatin, olaparib, and both in combination compared to the group without treatment (control) (p<0.05). Moreover, in both lines, a reduction in invasion rate was observed after treatment with carboplatin, olaparib and when combined, compared to the control group (p<0.05). CONCLUSION: Our data suggest that carboplatin and olaparib were able to block DNA repair and control the cancer invasion, especially when used in combination. The results with olaparib in the canine line are unpublished. The olaparib should be a possible agent against human breast cancer and canine mammary tumors.

Liquid biopsy can detect BRCA2 gene variants in female dogs with mammary neoplasia.

Mammary tumours (MT) are one of the most prevalent malignancies in female dogs and women. Currently, molecular analyzes have shown that each tumour type presents its own genetic signature. In this context, liquid biopsy allows a comprehensive genetic characterisation of the tumour, enabling early diagnosis and personalised treatment of patients. In women, deleterious mutations inherited in BRCA2 gene are associated with an increased risk of breast cancer, resistance to therapies and worse prognosis. In female dogs, there are many divergent data on the involvement of BRCA2 gene with mammary carcinogenesis and what its pathogenic potential is. Therefore, the objective was to identify BRCA2 gene variants in 20 plasma DNA samples, from 10 newly diagnosed dogs with mammary cancer (RD), five control (CTR) and five mastectomized patients. Eleven single nucleotide polymorphisms (SNPs) were detected, most of them in the exon 11 and two indels (deletion/insertion) in the BRCA2 gene. However, there was no statistically significant difference in the SNPs/indels detected between the groups. In addition, only one SNP (p.T1425P) and one deletion (p.L2307del) were considered deleterious using in silico computational models. Interestingly, most common variants were present in the plasma of all groups, except for the Ile2614Thr, Ile2614Val, Thr1425Pro and p.L2307del variants. Thus, we observed that SNPs are common in the BRCA2 gene of female dogs with MT, with a similar condition identified in women with breast cancer. Liquid biopsy approach in dogs with MT is useful for genetic and therapeutic proposals.